Efficacy and Safety of Longer-Term Administration of Evolocumab (AMG 145) in Patients With Hypercholesterolemia: 52-Week Results From the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) Randomized Trial

Study Questions:

Methods:

Of 1,359 randomized and dosed patients in the four evolocumab phase 2 parent studies, 1,104 (81%) elected to enroll into the OSLER (Open-Label Study of Long-term Evaluation Against LDL-C) trial. Regardless of their treatment assignment in the parent study, patients were randomized 2:1 to receive either open-label subcutaneous evolocumab 420 mg every 4 weeks with standard of care (SOC) (evolocumab + SOC, n = 736) or SOC alone (n = 368).

Results:

Ninety-two percent of patients in the evolocumab + SOC group and 89% of patients in the SOC group completed 52 weeks of follow-up. Patients who first received evolocumab in the OSLER study experienced a mean 52.3% [standard error (SE), 1.8%] reduction in low-density lipoprotein cholesterol (LDL-C) at week 52 (p < 0.0001). Patients who received one of six dosing regimens of evolocumab in the parent studies and received evolocumab + SOC in OSLER had persistent LDL-C reductions (mean reduction, 50.4% [SE, 0.8%] at the end of the parent study vs. 52.1% [SE, 1.0%] at 52 weeks; p = 0.31). In patients who discontinued evolocumab on entry into the OSLER study, LDL-C levels returned to near baseline levels. Adverse events and serious adverse events occurred in 81.4% and 7.1% of the evolocumab + SOC group patients and 73.1% and 6.3% of the SOC group patients, respectively.

Conclusions:

The authors concluded that evolocumab dosed every 4 weeks demonstrated continued efficacy and encouraging safety and tolerability over 1 year of treatment in hypercholesterolemic patients.

Perspective:

The findings from the OSLER study provide insight into the efficacy, safety, and tolerability of evolocumab treatment in hypercholesterolemic patients. Evolocumab reduced LDL-C on average by approximately 50% beyond the reduction achieved with optimal SOC in various hypercholesterolemic patient populations. The reductions in lipid levels achieved after 12 weeks were stable over the course of the study without evidence of attenuation. Conversely, discontinuation of evolocumab led to a fairly rapid return to baseline levels, but without a rebound phenomenon. Ongoing prospective outcomes trials will help further define the role of PCSK9 inhibitors as an emerging approach in the treatment of hypercholesterolemia.

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Efficacy and Safety of Longer-Term Administration of Evolocumab (AMG 145) in Patients With Hypercholesterolemia: 52-Week Results From the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) Randomized Trial